There were an estimated 220,900 new cases of prostate cancer (CaP) and 28,900 deaths in the US in 2003. Prostate cancer remains the most frequently diagnosed malignancy among North American males, and is second only to lung cancer in mortality. Genetics, diet, and lifestyle are just some of the factors that contribute to the development of prostate cancer. Prostate specific antigen (PSA) is the only prostate cancer marker widely used for population screening, diagnosis, and monitoring of prostate cancer (prostate cancer). The use of PSA as a serum marker has increased our ability to detect Prostate cancer, select therapy and to monitor outcomes.
Prostate cancer has proven to be a complicated disease due to its heterogeneous and multifocal nature. Consequently, much research has been devoted to elucidating the mechanisms of the disease. This has led to the construction of genetically engineered mouse models of prostate cancer utilizing transgenic and knock-out techniques that attempt to model the human clinical situation in all aspects. Rat probasin gene-based transgenic adenocarcinoma prostate (TRAMP) and LPB-SV40 tag (LADY) models are currently the most prevalent murine prostate cancer models.
Unlike in humans, murine models of prostate cancer currently lack established biomarkers for the disease, specifically serum biomarkers. Current prostate cancer (CaP) research in both basic and pre-clinical trial studies employ genetically engineered (GE) mouse models, since CaP does not occur naturally in rodents.
A serum biomarker in genetically engineered (GE)-CaP is valuable in four ways: it enables the non-invasive detection of cancer stage/progression; it can be used to assess effectiveness of treatments; it can monitor disease recurrence/disease-free state; and it is a much more affordable alternative than expensive molecular/micro-imaging techniques. The ability to non-invasively quantify tumor burden in living conditional tumor model mice will ultimately lead to the development of more accurate models of human cancer that are better suited to evaluating and optimizing preclinical cancer therapy.
Since mice do not produce and express a human PSA analog, the search begins for other equals in mice. Prostatic secretory protein of 94 amino acids (PSP94), also known as β-microseminoprotein (β-MSP) (Hara, M. and Kimura, H., J Lab .Clin. Med, 113: 541-548, 1989; Abrahamsson, P.-A. et al., The prostate, 12: 39-46, 1988; Hyakutake, H. et al., The prostate, 22: 347-355, 1993), is one of the three most abundantly secreted proteins from the prostate gland (the others being PSA and PAP [prostatic acid phosphatase]). Though PSP94 is an abundant protein, little is known about its real biological function. As with PSA, much research has investigated the utility of PSP94 as a prostate cancer marker in humans in terms of serum bound/free forms, urine levels and tissue expression. Furthermore, PSP94 expression in prostate tissue has been demonstrated as having statistical association with histological grade. In most cases this association is inversely correlated—that is, as tumor grade advances PSP94 expression decreases (Hyakutake, H. et al., The prostate, 22: 347-355, 1993)—the same as in PSA (Grande, M. et al., Clin. Cancer Res., 6: 1790-1795, 2000; Stege, R. et al., Clin. Cancer Res., 6: 160-165, 2000).
It would be highly desirable to be provided with a serum marker in rodent prostate cancer models.